Meniere?s Disease is one of the pathological entities characterized by endolymphatic hydrops of the cochlear and vestibular labyrinths. Hydrops can result from an alteration of ion transport properties of the epithelial cells bordering the endolymphatic system. Little is known about the cellular basis of the pathologic processes involved because data are lacking from normal as well as pathological systems concerning active and passive mechanisms of secretion and absorption of ions. Endolymph is unique in that it is the only extracellular fluid in the body with a high potassium (K+) concentration and low sodium (Na+) and calcium (Ca2+) concentrations. It is proposed to study the ion transport processes responsible for fluxes of K+, Na+ and Ca2+ in the vestibular labyrinth and cochlea, specifically vestibular dark cells (VDC) and strial marginal cells (SMC), by further utilization of electrophysiologic techniques and in vitro preparations developed in this laboratory. Specific goals to be addressed by the proposed studies include determining a) the generator of endocochlear potential (EP) and cellular signaling pathways controlling K+ secretion by stria vascularis; b) cellular pathways mediating Ca2+ secretion and absorption; c) cellular pathways mediating control of Na+ and K+ absorption; and d) cellular pathways mediating control of Cl and HCO3 secretion and absorption. Specific parameters to be measured include transepithelial voltage and resistance with the micro-Ussing chamber, transepithelial fluxes of K+, Cl- and Ca2+ with ion- selective vibrating probes, and electrical properties of cell membranes with several configurations of the patch clamp technique. The completion of this project will further our understanding of the processes controlling secretion and absorption of medically-important ions in the inner ear and may provide a foundation for the pharmacological management of inner ear disorders such as genetically-based syndromes and Meniere?s disease.